Acute damage to the central nervous system caused by stroke or trauma is the most frequent neurologic cause of death and disability. We hypothesize that the responses to these types of injury share common mechanisms that can serve as the basis for new therapeutic approaches. Since August 1990, when this program began, we have been cooperating in an effort to develop new types of therapies. The common theme we have been pursuing concerns the effects of neurotropic factors in models of central nervous system injury. At a cellular level, the impacts of stroke and traumatic injuries are similar. Both cause death and degeneration of some neurons and this is followed by reactive tissue changes. These reactions include sprouting of remaining neurons, and new growth of the supporting structures including glia and blood vessels. A class of substances known to respond to tissue damage in other parts of the body is growth factors (which include neurotrophic factors in the brain). These factors seem an especially important group since they are apparently required for the survival and maintenance of various types of neurons. Our ultimate goals are to develop methods of therapy that are likely to be more effective than prevailing techniques. Using animal models of central nervous system ischemia and trauma, we intend to: 1) determine the sequence of some critical events, at a biochemical level, occurring during the early phases of traumatic or ischemic injury, and 2) evaluate the effects of several types of neurotrophic factors and other related molecules in preventing damage and restoring function. We anticipate these studies will give us insights into the natural responses of the central nervous system to acute damage. These investigations will help us learn to augment the reparative processes, and inhibit dysfunctional responses. This will provide a scientific basis for selecting treatments. Some of these therapies should prevent or minimize neurologic damage at the time of injury. Other treatments have the potential to restore function to areas in which irreversible damage has already occurred.